Phase 1a is a dose escalation to evaluate the safety and tolerability of NX-2127 in adult patients with relapsed/refractory (R/R) B-cell malignancies, who have required and received at least 2 prior systemic therapies (or at least 1 prior therapy for patients with WM or PCNSL) and for whom no other therapies are known to provide clinical benefit. Phase 1b will investigate the efficacy of NX-2127 at the dosage(s) selected in Phase 1a in up to 5 cohorts of patients with R/R B-cell malignancy indications who have received at least 2 prior systemic therapies (or at least 1 prior therapy for patients with WM or PCNSL):

Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) with no BTK C481 mutation
BTK C481 mutation-positive CLL/SLL
Mantle Cell Lymphoma (MCL)
Follicular lymphoma (FL) or Marginal Zone Lymphoma (MZL); or Primary Central Nervous System Lymphoma (PCNSL)
Diffuse Large B-cell Lymphoma (DLBCL) or Waldenstrom Macroglobulinemia (WM)

Phase 1a is a dose escalation to evaluate the safety and tolerability of NX-5948 in adult patients with relapsed/refractory (R/R) B cell malignancies who have received at least 2 prior lines of therapy and for whom no other therapies are known to provide clinical benefit. Indications include: Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL), non-germinal center B-cell subtype (non-GCB) Diffuse Large B-cell Lymphoma (DLBCL), Mantle Cell Lymphoma (MCL), Waldenstrom Macroglobulinemia (WM), Marginal Zone Lymphoma (MZL), Follicular Lymphoma (FL) including those with secondary CNS involvement in any disease indication listed, or Primary Central Nervous System Lymphoma (PCNSL).

Phase 1b will investigate the efficacy of NX-5948 at the dose(s) selected in Phase 1a in up to 4 cohorts of patients with histologically confirmed R/R B-cell malignancy indications who have received at least 2 prior lines of therapy (or at least 1 prior line for patients with WM or PCNSL):

CLL or SLL including those with secondary CNS involvement of their disease
Non-GCB DLBCL or MCL including those with secondary CNS involvement of their disease
MZL, WM, or FL including those with secondary CNS involvement of their disease
PCNSL